TSC is a rare genetic disease that causes the growth of various non-cancerous tumors in the brain, kidney and other vital organs. It affects as many as 40,000 patients in the United States, with an estimated 70 to 80 percent developing kidney problems. TSC generally causes multiple tumors in both kidneys that compress normal kidney tissues as they increase in size, leading to kidney failure and bleeding.

A pill taken once daily, Afinitor blocks the uncontrolled activity of a certain protein, the mTOR kinase, which plays a critical role in the development and growth of the various non-cancerous tumors occurring in patients with TSC.

The FDA granted Afinitor orphan drug designations to treat renal angiomyolipomas and a certain type of brain tumor called subependymal giant cell astrocytoma (SEGA) in patients with TSC in 2009. An orphan designation is given to a drug intended to treat a disease or condition affecting fewer than 200,000 patients in the United States and for which the drug, based on supporting data, has shown promise in the treatment of the disease.

The drug’s application was granted priority review, a designation given to drugs that offer major advancements in treatment or provide a treatment where no adequate therapy exists. FDA completed review of this application in four months.

“This approval underscores the FDA’s commitment to the development of drugs for rare diseases with significant unmet medical needs,” said Richard Pazdur, M.D., director of the Office of Hematology and Oncology Products in the FDA’s Center for Drug Evaluation and Research. “It also represents another example of where an understanding of a disease’s underlying biology can lead to more selective drug development.”

Afinitor’s safety and efficacy were established in a double-blind, placebo-controlled clinical trial of 118 patients. Two-thirds of the patients were randomly chosen to receive Afinitor and one-third was assigned to receive a placebo. Patients were to be treated for up to four years, but patients receiving the placebo were offered Afinitor treatment if their kidney tumors grew while on study.

All patients had tumors in both kidneys, and about 40 percent had undergone a procedure to control bleeding from the tumors. The trial was designed to measure the percentage of patients whose tumor shrank or disappeared after treatment. With half of the patients receiving less than eight months of treatment, 42 percent treated with Afinitor showed a substantial reduction in tumor size lasting, on average, more than five months. None of those receiving placebo had tumor shrinkage.

Afinitor also was granted accelerated approval for this indication because early results showed a high rate of tumor reduction that lasted for several months. As part of this approval, Afinitor’s manufacturer must continue to follow the patients for at least four years to determine the duration of these responses and how responses affect the need for surgery and the control of the disease.

The most common side effects with Afinitor were inflamed or sore mouth, nausea or vomiting, skin problems (acne or eczema), cough, headache, diarrhea, abdominal pain, joint pains, swelling of legs or arms, and upper respiratory infection. Additionally, 15 percent of female patients receiving Afinitor had one or more missed menstrual periods during the study.

The FDA has previously approved Afinitor to treat patients with advanced renal cell carcinoma that has progressed after treatment with other cancer therapies; SEGA associated with TSC in patients who require treatment but are not candidates for surgical removal of the tumor; and progressive neuroendocrine tumors located in the pancreas that cannot be removed by surgery or that have spread to other parts of the body.

Afinitor is marketed by East Hanover, N.J.-based Novartis.

For more information:

FDA: Office of Hematology and Oncology Products

FDA: Approved Drugs: Questions and Answers

The FDA, an agency within the U.S. Department of Health and Human Services, protects the public health by assuring the safety, effectiveness, and security of human and veterinary drugs, vaccines and other biological products for human use, and medical devices. The agency also is responsible for the safety and security of our nation’s food supply, cosmetics, dietary supplements, products that give off electronic radiation, and for regulating tobacco products.